Diabetes Drug "Supertrialists" Dominate Literature

Miriam E Tucker

July 07, 2015

Just 110 authors contributed to a third of all published randomized clinical trials of diabetes drugs over a 20-year period, while 11 "supertrialists" were responsible for 10% of all the articles, according to a new study.

"Some authors…are far more active than others, to the extent that their names seem to pop out of every diabetes journal you open....While commending their industry, we would suggest that...the burden of authorship should perhaps be distributed more equitably in [the] future," Dr Frits Holleman, associate professor in the department of internal medicine, Academic Medical Center, Amsterdam, the Netherlands, and colleagues write in their report, published online July 1 in the BMJ.

The top 110 authors were involved in a total of 991 randomized clinical trials for diabetes during 1993–2013, with a median of 20 trials per author. Most of the trials (91%) were commercially sponsored, and 75% had at least one pharmaceutical company employee as an author.

In an accompanying editorial, Elizabeth Wager, PhD, a freelance publications consultant, says that the study "highlights the potential for distortion in the evidence base for diabetes drugs. Having 0.8% of authors responsible for one in three articles describing randomized controlled trials — and therefore providing the main evidence on a class of drugs — suggests a serious imbalance of power."

The paper doesn't provide the names of the individual "supertrialists."

Asked to comment, John B Buse, MD, PhD, professor of medicine and chief of the division of endocrinology at the University of North Carolina, Chapel Hill, told Medscape Medical News, "As someone who is probably on the list, I have no objection to the article. The numbers speak for themselves."

However, he continued, "I do think that the speculation about how and why people do this kind of work is off-target. There is a world-view that if science is paid for by a commercial interest that it is probably tainted and at least should be viewed with caution and…those people who have done that work should always be treated with suspicion of their motives."

Yet, he argues, "At least among the colleagues I work closely with in the US on multicenter trials, they do [take] this work very seriously, with great effort and tremendous integrity. Perhaps the article reflects a Eurocentric view?"

Findings About Top Authors

In their literature search, Dr Holleman and colleagues included randomized clinical trials for new drugs developed and subsequently marketed as diabetes treatments, including insulin analogs, meglitinides, thiazolidinediones, glucagonlike peptide 1 (GLP-1) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors.

Of a total 3782 articles during 1993–2013, the number published per year rose from 22 in 1993, to 70 in 2001, to 566 in 2013. A third (32%) of those papers involved the 110 top authors, whereas the other 13,482 authors contributed just one or two articles each.

Of the 110 top authors, 84 qualified based on total publications, 16 on frequent last authorship, and 10 on frequent first authorship. Half were from the United States, while 82% came from the United States, Italy, the United Kingdom, and Germany. A majority (56%) were affiliated with an academic institution, while 44% were employed by a pharmaceutical company.

The top 11 "supertrialists" included nine academics and two pharmaceutical-company employees. They were involved in a total of 354 randomized clinical trials, with a median of 42 each.

The most frequent journals for publication of the 991 studies from the top trialists were Diabetes Care, with 212, and Diabetes, Obesity, and Metabolism, with 143.

Of the total 704 articles for which conflicts of interest could be assessed, only 6% were fully independent (ie, had no commercial sponsor and no authors with reported conflicts of interest).

Just 25% of the papers reported the contributions of the various authors to the study. Medical writing assistance was reported in 44% of the total 991 trials, about half each by the sponsor itself or by a third party.

Reduce Reliance on Key Opinion Leaders (KOLs)

Dr Holleman and colleagues write, "It is easy to understand why pharmaceutical companies seek out the assistance of such well-published academic authors, for these have remarkable experience of diabetes treatment and the planning, execution, and presentation of clinical trials.

"They understand the expectations of clinicians and, not coincidentally, they are gifted communicators….However, the integrity of the evidence base for glucose-lowering drugs might suffer from the paucity of truly independent research and an overreliance of the diabetes community on a few authors from a few countries who have substantial conflicts of interest."

Both the study authors and the editorialist also question whether these prolific authors could have the time to adhere to the criteria for authorship laid out by the International Committee of Medical Journal Editors (ICMJE), which include "substantial contributions to the conception, design, data acquisition, data analysis, or data interpretation" and "drafting or revising the article" as well as final approval and accountability for the accuracy and integrity of the results.

"Is it possible to fulfill a strict interpretation of the ICMJE authorship criteria and report findings from a trial every other month?" Dr Wager wonders, adding that inconsistent application of the guidelines could mislead readers about who actually did the work.

And she says that while the use of properly acknowledged medical writers isn't necessarily a bad thing, the lack of access to such services by independent researchers could create a type of publication bias. "With greater support and therefore greater productivity, the views of industry-funded trialists will have a larger share of voice than those of independent clinicians and researchers."

She suggests that industry reexamine its reliance on the use of "key opinion leaders" and that research institutions consider rewarding investigators based on achievements other than publication numbers.

"We should also consider a radical overhaul of authorship guidelines (and rewards) to produce a new system that reflects current research practices [and] is regarded as equitable by all parties, trusted by the public, and uniformly interpreted and implemented," Dr Wager adds.

"Critical Mass" Needed for Such Trials

But Dr Buse says there are reasons for the academic "supertrialist" phenomenon.

"Should we select the people who do the trials and write the papers based on a lottery or limit investigators to just doing one or two trials at a time instead of the 10 or more that are generally necessary to achieve critical mass to be able to hire the regulatory and staff support to make this kind of work economically viable in an academic environment?"

He pointed out that only 20 to 50 people in the United States "have gone to the trouble to set up programs that are able to do this kind of work on anything but a small scale" and that his institution conducts investigator-initiated research and government-sponsored multicenter studies in addition to pharmaceutical company-funded trials.

"I do not see it as an imbalance of power or conflict of interest. My salary is determined by my department chair and is not dependent on industry-sponsored trials or consulting. I could stop doing all work with industry and would remain fully employed and perhaps even get a raise, [but] I would have to lay off about half of our staff," Dr Buse told Medscape Medical News.

He continued, "The big questions of the day can be answered only with multicenter clinical trials. I participate in them despite the fact that they are difficult [and] highly regulated…because someone has to or we will not get an answer. I honestly believe that our patients, whether engaged in trials or not, are glad we do them."

He added that the scientists who participate are highly motivated "and could make twice as much if they went to work for industry directly. But all of us do it because we believe that having independent patient-centered investigators and sites give us an opportunity to uniquely contribute to the efforts to answer important clinical and regulatory questions."

He concluded, "Of course I am biased and some may think even 'conflicted,' but I do think it is honorable and difficult work that we do quite well, no matter who pays for it and who ends up authoring the papers."

No outside funding was received for the study. Dr Holleman has received speaker fees and research support from Sanofi, MSD, Eli Lilly, AstraZeneca, and Janssen-Cilag in the past 3 years. Dr Wager provides consultancy and training on medical writing to universities, academic societies, publishers, and pharmaceutical companies and formerly worked as a medical writer for pharmaceutical companies. Dr Buse has served as an advisor or consultant for or has received grants for clinical research from Amylin Pharmaceuticals, Andromeda Biotech, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dance Biopharm, Elcelyx Therapeutics, Hoffmann-La Roche, GI Dynamics, Halozyme Therapeutics, Intarcia Therapeutics, Johnson & Johnson Pharmaceutical Research & Development, Lexicon Pharmaceuticals, Lilly, LipoScience, MacroGenics, Medtronic, Merck, Metavention, Novo Nordisk, Orexigen Therapeutics, Osiris Therapeutics, Pfizer, PhaseBio Pharmaceuticals, Quest Diagnostics, Sanofi, Takeda Pharmaceuticals North America, Tolerx, and TransTech Pharma. He also owns stock, stock options, or bonds in PhaseBio Pharmaceuticals.

BMJ. Published online July 1, 2015. Article, Editorial


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